Date of Completion
Honors College Thesis
Dr. William Falls
p38, conditioned fear, GSK3, inhibition, freezing
p38 mitogen activated protein kinase (p38) is a kinase that has been implicated in cellular plasticity, stress, and psychiatric disorders and recently in the process of DNA repair. Recently, we have shown that p38 is responsible for inhibiting Glycogen Synthase Kinase 3β (GSK3β), which has also been shown to be involved in the same processes and recently in the process of DNA repair. We have also shown that GSK3β is regulated by stress and that its inhibition produces exaggerated conditioned fear. The goal of this study is to examine whether inhibiting p38 will result in a similar exaggeration of conditioned fear. To this end, mice were injected systemically with the potent and selective inhibitor of p38, SB203580 or vehicle prior to tone and footshock fear conditioning and tested for freezing to the tone one day later. Mice injected with SB203580 showed greater tone freezing than mice injected with vehicle. In contrast to tone freezing, SB203580 injections did not affect freezing to the context. Injections of SB203580 prior to 24 hours after fear conditioning, but before fear testing, also did not affect freezing. These data suggest that p38 plays a role in regulating the strength of conditioned fear. The fact that p38 regulates GSK3β and that inhibition of GSK3β also produces exaggerated conditioned fear raises the possibility that a p38 to GSK3β pathway may be regulating the strength of conditioned fear.
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Bauman, Brittany Nicole and Falls, William Dr., "Role of p38 MAPK inhibitor in conditioned fear" (2015). UVM Honors College Senior Theses. 186.